Core C is the Animal Handling and Functional Analysis Core. This facility is located at the University of Chicago. This Core facility will receive animals directly from the Projects, including the Projects in Baltimore and Cincinnati. Animals will undergo functional analysis using a subset of the SHIRPA protocols that were developed for analysis of in vivo muscle function. Following this, materials from these mice will be made available to Core B, the Histopathology Core, for quantitative and qualitative analysis. A longstanding hypothesis in muscular dystrophy research is that loss of membrane integrity is a primary event leading to the degeneration of skeletal muscle fibers resulting in disease. Degeneration and necrosis of myofibers in diseased skeletal muscle induces release of cytokines, chemokines, and growth factors from neighboring myofibers, fibroblasts, and inflammatory cells that infiltrate into the tissue to remove cellular debris. Release of TGFB and related TGPB superfamily members, such as myostatin, is involved in this paracrine milieu that alters both myofiber growth, regeneration, and fibrosis in MD. Genetic models of muscular dystrophy have been of great importance in dissecting the molecular effectors that lead to this disease and alter its response. This core will provide functional analysis of these models and provide materials for pathological analysis to dissect signaling relationships in the TGFB super family in programming disease and fibrosis in muscular dystrophy. All three projects in the PPG will extensively use genetically modified mouse models to isolate single gene function to uncover new therapeutic opportunities. The Projects will also test new and existing drug to modify these pathways including soluble receptor and signaling inhibitors. This Core will analyze the results of these manipulations. The Core is an essential component for the success of the PPG.